ORIGINAL APPLICATION: This program project application represents a multi-investigator approach to selected immunologic and immunopathologic problems that pertain to pulmonary disease. The program consists of 5 projects and one electron microscopy core. The projects are grouped in the following categories: 1) Pathobiologic mechanisms and lung disease, 2) Host defense and Immunologic responses in the lung, and 3) Immunology of Sarcoidosis. In the first category emphasis will be placed on the roles of delayed hypersensitivity mediators, host originated hydrolases and proteases of Serratia and Pseudomonas; in addition, complement dependent neutrophil sequestration and mechanisms of tissue injury in shock lung will be studied. The second category will be concerned with animal models for studying the response of the lung to antigenic stimulation. Emphasis will be placed on cell-mediated and immunoglobulin responses and their function in bacterial pneumonias using animal models. The third category will be concerned with preparation of Kveim active material and the etiologic, immunologic and genetic aspects of sarcoidosis. SUPPLEMENTAL APPLICATION: A new project has been activated which will focus on shifts in the populations of bronchus associated lymphoid tissue (BALT) in the face of delayed hypersensitivity reactions in the lung. Analysis will include cell numbers, classification of Ig plus cells, T cells, null cells, etc. Cells harvested from BALT, hilar lymph node complex and cells in the airways (lavage) will be studied. The pattern of cellular migration through epithelium in airways will be elucidated. Funds are also requested to support a Core Laboratory for Preparative Biochemistry which provides technical support to 3 projects. The main emphasis of this laboratory will be to provide expertise in the purification and characterization of biologically active molecules.